5-135033813-TGGCGGC-TGGC

Variant names:

• chr5-135033813-TGGC-T
• rs752690307
• NM_002653.5:c.66_68delGCC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_002653.5(PITX1):​c.66_68delGCC​(p.Pro23del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000478 in 1,401,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: PITX1 NM_002653.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71

Genes affected

PITX1 (HGNC:9004): (paired like homeodomain 1) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. [provided by RefSeq, Jul 2008]

PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_002653.5. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAdExome4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5	c.66_68delGCC	p.Pro23del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000265340.12	NP_002644.4
PITX1	XM_047417318.1	c.168_170delGCC	p.Pro57del	disruptive_inframe_deletion	Exon 2 of 4		XP_047273274.1
PITX1-AS1	NR_161235.1	n.267+286_267+288delGGC		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12	c.66_68delGCC	p.Pro23del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000478 AC: 67 AN: 1401790 Hom.: 0 AF XY: 0.0000546 AC XY: 38 AN XY: 695550

Gnomad4 AFR exome AF: 0.0000340

Gnomad4 AMR exome AF: 0.000385

Gnomad4 ASJ exome AF: 0.0000809

Gnomad4 EAS exome AF: 0.000169

Gnomad4 SAS exome AF: 0.0000493

Gnomad4 FIN exome AF: 0.000207

Gnomad4 NFE exome AF: 0.0000257

Gnomad4 OTH exome AF: 0.0000516

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs752690307; hg19: chr5-134369503;